JPH0383985A - 新規４―メチレン―２―オキソ―８―アザスピロ〔４，５〕デカン誘導体，それらを含む医薬組成物およびそれらの調整方法 - Google Patents

新規４―メチレン―２―オキソ―８―アザスピロ〔４，５〕デカン誘導体，それらを含む医薬組成物およびそれらの調整方法

Info

Publication number: JPH0383985A
Authority: JP; Japan
Prior art keywords: formula; derivative; oxo; decane; methylene
Prior art date: 1989-08-10
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Pending

Application number

JP2209363A

Other languages

English (en)

Japanese (ja)

Inventor

Edit Toth

エディト　トーツ

Jozsef Toerley

ヨージェフ　トェルレイ

Sandor Goeroeg

サーンドル　ゴェロェグ

Laszlo Szporny

ラースロー　スポルニ

Bela Kiss

ベーラ　キッス

Eva Palosi

エバ　パーロシ

Dora Groo

ドーラ　グロー

Istvan Laszlovszky

イシュトバーン　ラスロブスキ

Erzsebet Lapis

エルジェーベト　ラピシュ

Ferenc Auth

フェレンツ　アウツ

Laszlo Gaal

ラースロー　ガール

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Richter Gedeon Nyrt

Richter Gedeon Vegyeszeti Gyar Nyrt

Original Assignee

Richter Gedeon Nyrt

Richter Gedeon Vegyeszeti Gyar RT

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1989-08-10

Filing date

1990-08-09

Publication date

1991-04-09

1990-08-09 Application filed by Richter Gedeon Nyrt, Richter Gedeon Vegyeszeti Gyar RT filed Critical Richter Gedeon Nyrt

1991-04-09 Publication of JPH0383985A publication Critical patent/JPH0383985A/ja

Status Pending legal-status Critical Current

Links

150000001875 compounds Chemical class 0.000 title claims description 61
238000002360 preparation method Methods 0.000 title claims description 11
DIOQZVSQGTUSAI-NJFSPNSNSA-N decane Chemical class CCCCCCCCC[14CH3] DIOQZVSQGTUSAI-NJFSPNSNSA-N 0.000 title claims description 8
229940079593 drug Drugs 0.000 title description 4
239000003814 drug Substances 0.000 title description 4
DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 claims description 38
238000000034 method Methods 0.000 claims description 36
239000000203 mixture Substances 0.000 claims description 30
239000002253 acid Substances 0.000 claims description 29
150000003839 salts Chemical class 0.000 claims description 28
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 28
239000002904 solvent Substances 0.000 claims description 22
239000004480 active ingredient Substances 0.000 claims description 17
238000006243 chemical reaction Methods 0.000 claims description 17
150000003242 quaternary ammonium salts Chemical class 0.000 claims description 15
239000002585 base Substances 0.000 claims description 13
-1 methylsulfonyloxy Chemical group 0.000 claims description 13
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims description 12
229910052736 halogen Inorganic materials 0.000 claims description 10
150000002367 halogens Chemical class 0.000 claims description 10
CYCSGNGCLXFNFZ-UHFFFAOYSA-N (4-ethynylpiperidin-4-yl) carbamate Chemical class NC(=O)OC1(C#C)CCNCC1 CYCSGNGCLXFNFZ-UHFFFAOYSA-N 0.000 claims description 9
239000001257 hydrogen Substances 0.000 claims description 9
229910052739 hydrogen Inorganic materials 0.000 claims description 9
239000011541 reaction mixture Substances 0.000 claims description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 7
125000000217 alkyl group Chemical group 0.000 claims description 7
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
239000001301 oxygen Substances 0.000 claims description 7
229910052760 oxygen Inorganic materials 0.000 claims description 7
239000008194 pharmaceutical composition Substances 0.000 claims description 7
238000007363 ring formation reaction Methods 0.000 claims description 7
SKGCHBGIBOPGHV-UHFFFAOYSA-N 1,3-dioxolan-2-imine Chemical class N=C1OCCO1 SKGCHBGIBOPGHV-UHFFFAOYSA-N 0.000 claims description 6
125000002837 carbocyclic group Chemical group 0.000 claims description 6
239000003795 chemical substances by application Substances 0.000 claims description 6
150000002431 hydrogen Chemical group 0.000 claims description 6
239000012948 isocyanate Substances 0.000 claims description 6
150000002513 isocyanates Chemical class 0.000 claims description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 5
BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 claims description 5
GVZFMFFUAZKMOB-UHFFFAOYSA-N 4-ethynylpiperidin-4-ol Chemical class C#CC1(O)CCNCC1 GVZFMFFUAZKMOB-UHFFFAOYSA-N 0.000 claims description 5
230000002378 acidificating effect Effects 0.000 claims description 5
125000003545 alkoxy group Chemical group 0.000 claims description 5
125000003118 aryl group Chemical group 0.000 claims description 5
150000004677 hydrates Chemical class 0.000 claims description 5
238000009835 boiling Methods 0.000 claims description 4
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 4
229910000041 hydrogen chloride Inorganic materials 0.000 claims description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
208000020016 psychiatric disease Diseases 0.000 claims description 4
239000012453 solvate Substances 0.000 claims description 4
239000011230 binding agent Substances 0.000 claims description 3
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 3
229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
125000004953 trihalomethyl group Chemical group 0.000 claims description 3
BSORSXKISMDECI-UHFFFAOYSA-N 8-[4,4-bis(4-fluorophenyl)but-3-enyl]-4-methylidene-1,3-dioxa-8-azaspiro[4.5]decan-2-one Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)=CCCN1CCC2(C(OC(=O)O2)=C)CC1 BSORSXKISMDECI-UHFFFAOYSA-N 0.000 claims description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
239000000654 additive Substances 0.000 claims description 2
125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims description 2
125000005279 aryl sulfonyloxy group Chemical group 0.000 claims description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
229910052794 bromium Inorganic materials 0.000 claims description 2
239000000460 chlorine Substances 0.000 claims description 2
229910052801 chlorine Inorganic materials 0.000 claims description 2
239000012458 free base Substances 0.000 claims description 2
150000002576 ketones Chemical class 0.000 claims description 2
239000000126 substance Substances 0.000 claims 8
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 4
ASPBBYVNTMIKLA-UHFFFAOYSA-N 2,8-diazaspiro[4.5]decan-3-one Chemical class C1NC(=O)CC21CCNCC2 ASPBBYVNTMIKLA-UHFFFAOYSA-N 0.000 claims 3
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 2
SEUNTAIZLCAWDW-UHFFFAOYSA-N 1-oxa-8-azaspiro[4.5]decan-2-one Chemical class O1C(=O)CCC11CCNCC1 SEUNTAIZLCAWDW-UHFFFAOYSA-N 0.000 claims 1
TWPXZBMZJBTTKI-UHFFFAOYSA-N 3-benzyl-8-[4,4-bis(4-fluorophenyl)but-3-enyl]-4-methylidene-1-oxa-3,8-diazaspiro[4.5]decan-2-one Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)=CCCN1CCC2(C(N(CC=3C=CC=CC=3)C(=O)O2)=C)CC1 TWPXZBMZJBTTKI-UHFFFAOYSA-N 0.000 claims 1
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 1
GEMSTPWCYFPJOS-UHFFFAOYSA-N 4-methylidene-8-azaspiro[4.5]decan-2-one Chemical class C=C1CC(=O)CC11CCNCC1 GEMSTPWCYFPJOS-UHFFFAOYSA-N 0.000 claims 1
ZLTAEWBDEBSYLT-UHFFFAOYSA-N 8-[4,4-bis(4-fluorophenyl)but-3-enyl]-4-methylidene-1-oxa-3,8-diazaspiro[4.5]decan-2-one Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)=CCCN1CCC2(C(NC(=O)O2)=C)CC1 ZLTAEWBDEBSYLT-UHFFFAOYSA-N 0.000 claims 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
239000003085 diluting agent Substances 0.000 claims 1
238000009472 formulation Methods 0.000 claims 1
230000003204 osmotic effect Effects 0.000 claims 1
239000003002 pH adjusting agent Substances 0.000 claims 1
239000003381 stabilizer Substances 0.000 claims 1
239000012929 tonicity agent Substances 0.000 claims 1
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 51
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 39
239000000243 solution Substances 0.000 description 19
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
239000003826 tablet Substances 0.000 description 11
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
239000000047 product Substances 0.000 description 9
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
241001465754 Metazoa Species 0.000 description 8
238000001704 evaporation Methods 0.000 description 8
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
238000003756 stirring Methods 0.000 description 8
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
239000012153 distilled water Substances 0.000 description 6
230000008020 evaporation Effects 0.000 description 6
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
229910052757 nitrogen Inorganic materials 0.000 description 6
239000003960 organic solvent Substances 0.000 description 6
239000000725 suspension Substances 0.000 description 6
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 5
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 5
229960004046 apomorphine Drugs 0.000 description 5
VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 5
229910052786 argon Inorganic materials 0.000 description 5
239000008101 lactose Substances 0.000 description 5
239000007858 starting material Substances 0.000 description 5
238000012360 testing method Methods 0.000 description 5
239000008096 xylene Substances 0.000 description 5
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
235000011054 acetic acid Nutrition 0.000 description 4
150000007933 aliphatic carboxylic acids Chemical class 0.000 description 4
230000000561 anti-psychotic effect Effects 0.000 description 4
QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 4
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
230000000694 effects Effects 0.000 description 4
150000002170 ethers Chemical class 0.000 description 4
238000001914 filtration Methods 0.000 description 4
230000007935 neutral effect Effects 0.000 description 4
150000007530 organic bases Chemical group 0.000 description 4
239000012071 phase Substances 0.000 description 4
DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
208000009132 Catalepsy Diseases 0.000 description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 3
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 3
UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
241000700159 Rattus Species 0.000 description 3
229920002472 Starch Polymers 0.000 description 3
206010047853 Waxy flexibility Diseases 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
125000001931 aliphatic group Chemical group 0.000 description 3
150000004945 aromatic hydrocarbons Chemical class 0.000 description 3
230000006399 behavior Effects 0.000 description 3
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
239000002775 capsule Substances 0.000 description 3
239000000969 carrier Substances 0.000 description 3
239000003054 catalyst Substances 0.000 description 3
235000015165 citric acid Nutrition 0.000 description 3
229960004170 clozapine Drugs 0.000 description 3
238000001816 cooling Methods 0.000 description 3
230000018044 dehydration Effects 0.000 description 3
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239000008298 dragée Substances 0.000 description 3
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239000000796 flavoring agent Substances 0.000 description 3
235000019634 flavors Nutrition 0.000 description 3
235000019359 magnesium stearate Nutrition 0.000 description 3
239000000546 pharmaceutical excipient Substances 0.000 description 3
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
229920000053 polysorbate 80 Polymers 0.000 description 3
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238000001953 recrystallisation Methods 0.000 description 3
238000010992 reflux Methods 0.000 description 3
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229910052623 talc Inorganic materials 0.000 description 3
229910002012 Aerosil® Inorganic materials 0.000 description 2
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
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235000011034 Rubus glaucus Nutrition 0.000 description 2
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WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
229910052783 alkali metal Inorganic materials 0.000 description 2
150000004703 alkoxides Chemical class 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
230000003542 behavioural effect Effects 0.000 description 2
HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 2
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238000002474 experimental method Methods 0.000 description 2
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229910000042 hydrogen bromide Inorganic materials 0.000 description 2
238000001727 in vivo Methods 0.000 description 2
230000001939 inductive effect Effects 0.000 description 2
239000011261 inert gas Substances 0.000 description 2
239000004615 ingredient Substances 0.000 description 2
230000005764 inhibitory process Effects 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
239000000314 lubricant Substances 0.000 description 2
238000005259 measurement Methods 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
239000012074 organic phase Substances 0.000 description 2
TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 2
238000007911 parenteral administration Methods 0.000 description 2
239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
229920001592 potato starch Polymers 0.000 description 2
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/10—Spiro-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

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Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Life Sciences & Earth Sciences (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
General Chemical & Material Sciences (AREA)
Psychiatry (AREA)
Anesthesiology (AREA)
Hospice & Palliative Care (AREA)
Pain & Pain Management (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Hydrogenated Pyridines (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Investigating Or Analyzing Non-Biological Materials By The Use Of Chemical Means (AREA)

JP2209363A 1989-08-10 1990-08-09 新規４―メチレン―２―オキソ―８―アザスピロ〔４，５〕デカン誘導体，それらを含む医薬組成物およびそれらの調整方法 Pending JPH0383985A (ja)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
HU894094A HU204276B (en)	1989-08-10	1989-08-10	Process for producing new 1-oxa-2-oxo-4-methylen-8-aza-spiro(4,5)decane derivatives and pharmaceutical compositions containing them
HU4094/89		1989-08-10

Publications (1)

Publication Number	Publication Date
JPH0383985A true JPH0383985A (ja)	1991-04-09

Family

ID=10966866

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
JP2209363A Pending JPH0383985A (ja)	1989-08-10	1990-08-09	新規４―メチレン―２―オキソ―８―アザスピロ〔４，５〕デカン誘導体，それらを含む医薬組成物およびそれらの調整方法
JP2209362A Pending JPH0381277A (ja)	1989-08-10	1990-08-09	２―オキソ―３，８―ジアザスピロ〔４，５〕デカン誘導体，それを含む医薬組成物及びその製造方法

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
JP2209362A Pending JPH0381277A (ja)	1989-08-10	1990-08-09	２―オキソ―３，８―ジアザスピロ〔４，５〕デカン誘導体，それを含む医薬組成物及びその製造方法

Country Status (26)

Country	Link
US (2)	US5132303A (2)
EP (2)	EP0413516B1 (2)
JP (2)	JPH0383985A (2)
KR (2)	KR940002826B1 (2)
CN (1)	CN1025031C (2)
AT (2)	ATE104671T1 (2)
AU (2)	AU621238B2 (2)
CA (2)	CA2023018C (2)
DD (2)	DD299431A5 (2)
DE (2)	DE69014008T2 (2)
DK (1)	DK0413516T3 (2)
ES (2)	ES2052179T3 (2)
FI (1)	FI93456C (2)
HK (1)	HK118295A (2)
HU (2)	HU206677B (2)
IE (1)	IE902885A1 (2)
IL (2)	IL95325A (2)
IN (1)	IN170979B (2)
IS (1)	IS3612A7 (2)
MY (1)	MY107240A (2)
NO (1)	NO903511L (2)
NZ (2)	NZ234843A (2)
PL (2)	PL163899B1 (2)
SG (1)	SG59864G (2)
YU (2)	YU150489A (2)
ZA (3)	ZA906299B (2)

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0279990B1 (en) *	1986-12-17	1995-07-12	Glaxo Group Limited	Use of heterocyclic derivatives in the treatment of cognitive disorders
YU150489A (sh) *	1989-08-10	1992-12-21	W.L. Gore & Co. Gmbh.	Uređaj za ispitivanje odevnih predmeta na nepromočivost
HU204529B (en) *	1989-08-10	1992-01-28	Richter Gedeon Vegyeszet	Process for producing new 1-oxa-2-oxo-8-aza-spiro(4,5)decane derivatives and pharmaceutical compositions containing them
US5534520A (en) *	1990-04-10	1996-07-09	Fisher; Abraham	Spiro compounds containing five-membered rings
US5852029A (en) *	1990-04-10	1998-12-22	Israel Institute For Biological Research	Aza spiro compounds acting on the cholinergic system with muscarinic agonist activity
EP0492020A1 (en) *	1990-12-21	1992-07-01	Merrell Dow Pharmaceuticals Inc.	Use of certain esters of hexahydro-8-hydroxy-2,6-methano-2H-quinolizin-3(4H)-one and related compounds for treating cognitive disorders
GB9206989D0 (en) *	1992-03-31	1992-05-13	Glaxo Group Ltd	Chemical compounds
US5756743A (en) *	1996-04-10	1998-05-26	Hoechst Marion Roussel Inc.	Spiro cyclopent b!indole-piperidines!
US6100256A (en) *	1996-12-02	2000-08-08	Merck Sharp & Dohme Ltd.	Use of NK-1 receptors antagonists for treating schizophrenic disorders
US6974825B1 (en)	1996-12-20	2005-12-13	Astrazeneca Canada Inc.	Compounds with analgesic effect
SE9604786D0 (sv)	1996-12-20	1996-12-20	Astra Pharma Inc	New compounds
SE9904675D0 (sv)	1999-12-20	1999-12-20	Astra Pharma Inc	Novel compounds
SE0101769D0 (sv)	2001-05-18	2001-05-18	Astrazeneca Ab	Novel compounds
SE0101771D0 (sv)	2001-05-18	2001-05-18	Astrazeneca Ab	Novel compounds
SE0101770D0 (sv) *	2001-05-18	2001-05-18	Astrazeneca Ab	Novel compounds
SE0101773D0 (sv) *	2001-05-18	2001-05-18	Astrazeneca Ab	Novel compounds
KR20030087248A (ko) *	2002-05-08	2003-11-14	(주)씨엔아이	온라인을 통한 상거래 기초항목의 설정기능을 갖는 상거래관리장치
WO2010147776A1 (en) *	2009-06-16	2010-12-23	Merck Sharp & Dohme Corp.	Substituted -1,3,8-triazaspiro[4.5]decane-2,4-diones
GB201416352D0 (en) *	2014-09-16	2014-10-29	Shire Internat Gmbh	Spirocyclic derivatives
GB201416346D0 (en) *	2014-09-16	2014-10-29	Shire Internat Gmbh	Spirocyclic derivatives

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
NL127065C (2) *	1964-04-22
CH601304A5 (2) *	1974-02-12	1978-07-14	Buskine Sa
BE790675A (fr) *	1971-10-29	1973-04-27	Science Union & Cie	Nouveaux derives de l'oxa-1 diaza-3,8 spiro (4,5) decane
FR2615515B1 (fr) *	1987-05-22	1989-06-30	Adir	Nouveaux derives du spiro 4, 5 decane, leur procede de preparation et les compositions pharmaceutiques les renfermant
YU150489A (sh) *	1989-08-10	1992-12-21	W.L. Gore & Co. Gmbh.	Uređaj za ispitivanje odevnih predmeta na nepromočivost
HU204529B (en) *	1989-08-10	1992-01-28	Richter Gedeon Vegyeszet	Process for producing new 1-oxa-2-oxo-8-aza-spiro(4,5)decane derivatives and pharmaceutical compositions containing them
HU204530B (en) *	1989-08-10	1992-01-28	Richter Gedeon Vegyeszet	Process for producing new 1-oxa-2-oxo-8-aza-spiro(4,5)decane derivatives and pharmaceutical compositions containing them

1989
- 1989-07-27 YU YU150489A patent/YU150489A/sh unknown
- 1989-08-10 HU HU903233A patent/HU206677B/hu not_active IP Right Cessation
- 1989-08-10 HU HU894094A patent/HU204276B/hu not_active IP Right Cessation
1990
- 1990-08-08 KR KR1019900012168A patent/KR940002826B1/ko not_active Expired - Fee Related
- 1990-08-08 KR KR1019900012169A patent/KR940000830B1/ko not_active Expired - Fee Related
- 1990-08-09 AT AT9090308783T patent/ATE104671T1/de not_active IP Right Cessation
- 1990-08-09 ZA ZA906299A patent/ZA906299B/xx unknown
- 1990-08-09 NZ NZ234843A patent/NZ234843A/en unknown
- 1990-08-09 NO NO90903511A patent/NO903511L/no unknown
- 1990-08-09 EP EP90308783A patent/EP0413516B1/en not_active Expired - Lifetime
- 1990-08-09 AT AT90308779T patent/ATE113951T1/de not_active IP Right Cessation
- 1990-08-09 IN IN687/CAL/90A patent/IN170979B/en unknown
- 1990-08-09 SG SG1995903969A patent/SG59864G/en unknown
- 1990-08-09 DE DE69014008T patent/DE69014008T2/de not_active Expired - Fee Related
- 1990-08-09 EP EP90308779A patent/EP0412821B1/en not_active Expired - Lifetime
- 1990-08-09 AU AU60804/90A patent/AU621238B2/en not_active Ceased
- 1990-08-09 YU YU154090A patent/YU154090A/sh unknown
- 1990-08-09 DD DD90343359A patent/DD299431A5/de not_active IP Right Cessation
- 1990-08-09 IL IL9532590A patent/IL95325A/en not_active IP Right Cessation
- 1990-08-09 ZA ZA906300A patent/ZA906300B/xx unknown
- 1990-08-09 DK DK90308783.1T patent/DK0413516T3/da active
- 1990-08-09 ZA ZA906304A patent/ZA906304B/xx unknown
- 1990-08-09 DE DE69008275T patent/DE69008275T2/de not_active Expired - Fee Related
- 1990-08-09 AU AU60803/90A patent/AU621771B2/en not_active Ceased
- 1990-08-09 DD DD90343354A patent/DD299428A5/de not_active IP Right Cessation
- 1990-08-09 IS IS3612A patent/IS3612A7/is unknown
- 1990-08-09 IL IL9532490A patent/IL95324A/en not_active IP Right Cessation
- 1990-08-09 CA CA002023018A patent/CA2023018C/en not_active Expired - Fee Related
- 1990-08-09 ES ES90308783T patent/ES2052179T3/es not_active Expired - Lifetime
- 1990-08-09 NZ NZ234846A patent/NZ234846A/en unknown
- 1990-08-09 CA CA002023015A patent/CA2023015A1/en not_active Abandoned
- 1990-08-09 IE IE288590A patent/IE902885A1/en unknown
- 1990-08-09 ES ES90308779T patent/ES2063923T3/es not_active Expired - Lifetime
- 1990-08-09 JP JP2209363A patent/JPH0383985A/ja active Pending
- 1990-08-09 JP JP2209362A patent/JPH0381277A/ja active Pending
- 1990-08-10 US US07/566,278 patent/US5132303A/en not_active Expired - Fee Related
- 1990-08-10 MY MYPI90001343A patent/MY107240A/en unknown
- 1990-08-10 US US07/566,279 patent/US5132309A/en not_active Expired - Fee Related
- 1990-08-10 PL PL90286443A patent/PL163899B1/pl unknown
- 1990-08-10 FI FI903974A patent/FI93456C/fi not_active IP Right Cessation
- 1990-08-10 PL PL90291648A patent/PL164662B1/pl unknown
- 1990-08-10 CN CN90106974A patent/CN1025031C/zh not_active Expired - Fee Related
1995
- 1995-07-20 HK HK118295A patent/HK118295A/en not_active IP Right Cessation

Also Published As

Publication number	Publication date
ZA906299B (en)	1991-06-26
HUT59375A (en)	1992-05-28
DD299431A5 (de)	1992-04-16
DE69014008D1 (de)	1994-12-15
US5132303A (en)	1992-07-21
SG59864G (en)	1995-09-01
YU150489A (sh)	1992-12-21
EP0412821A2 (en)	1991-02-13
HU903233D0 (en)	1990-10-28
NZ234846A (en)	1992-03-26
DK0413516T3 (da)	1994-05-24
EP0412821B1 (en)	1994-11-09
FI903974A0 (fi)	1990-08-10
ATE113951T1 (de)	1994-11-15
ATE104671T1 (de)	1994-05-15
ZA906300B (en)	1991-05-29
US5132309A (en)	1992-07-21
AU6080390A (en)	1991-02-14
EP0413516A2 (en)	1991-02-20
ES2052179T3 (es)	1994-07-01
NZ234843A (en)	1992-03-26
NO903511D0 (no)	1990-08-09
PL286443A1 (en)	1992-01-13
ES2063923T3 (es)	1995-01-16
IL95324A (en)	1994-02-27
CA2023015A1 (en)	1991-02-11
IL95325A0 (en)	1991-06-30
DE69014008T2 (de)	1995-03-23
KR910004631A (ko)	1991-03-29
AU621238B2 (en)	1992-03-05
PL163899B1 (pl)	1994-05-31
CN1025031C (zh)	1994-06-15
HUT55785A (en)	1991-06-28
KR910004630A (ko)	1991-03-29
HK118295A (en)	1995-07-28
IL95324A0 (en)	1991-06-30
DE69008275T2 (de)	1994-08-04
IE902885A1 (en)	1991-02-27
FI93456B (fi)	1994-12-30
IS3612A7 (is)	1991-02-11
CN1049349A (zh)	1991-02-20
AU621771B2 (en)	1992-03-19
CA2023018A1 (en)	1991-02-11
CA2023018C (en)	1995-11-28
IL95325A (en)	1994-06-24
AU6080490A (en)	1991-02-14
ZA906304B (en)	1991-06-26
HU204276B (en)	1991-12-30
EP0413516B1 (en)	1994-04-20
KR940002826B1 (ko)	1994-04-04
EP0413516A3 (en)	1991-11-27
PL291648A1 (en)	1992-06-01
IN170979B (2)	1992-06-27
DE69008275D1 (de)	1994-05-26
KR940000830B1 (ko)	1994-02-02
EP0412821A3 (en)	1991-11-27
HU206677B (en)	1992-12-28
PL164662B1 (pl)	1994-09-30
DD299428A5 (de)	1992-04-16
NO903511L (no)	1991-02-11
YU154090A (sh)	1992-12-21
MY107240A (en)	1995-10-31
FI93456C (fi)	1995-04-10
JPH0381277A (ja)	1991-04-05

Publication	Publication Date	Title
JPH0383985A (ja)	1991-04-09	新規４―メチレン―２―オキソ―８―アザスピロ〔４，５〕デカン誘導体，それらを含む医薬組成物およびそれらの調整方法
US4590189A (en)	1986-05-20	Condensed pyrrolinone derivatives, their production and use
US5252584A (en)	1993-10-12	Hydroxyquinolone derivatives
CS277611B6 (en)	1993-03-17	3-(2,2,5,6-tetrahydropyridyl)-pyrrolopyridine derivatives
JPH0412269B2 (2)	1992-03-04
AU597326B2 (en)	1990-05-31	New derivatives of decahydroquinoline,their preparation process, the preparation intermediates, their use as medicaments and the compositions containing them
EP0623621A1 (en)	1994-11-09	Oxazabicyclo derivatives and their use as 5-HT4 receptor agonists
KR0178469B1 (ko)	1999-03-20	흥분성 아미노산 길항제
US5118693A (en)	1992-06-02	4,4-disubstituted piperidine derivatives, pharmaceutical compositions containing them and process for preparing same
EP0328700A1 (en)	1989-08-23	4,7-Dihydropyrazolo(1,5-a)pyrimidine compound and pharmaceutical use thereof
NL8002656A (nl)	1980-11-11	Gesubstitueerde pyrido 1.2-a pyrimidinen.
KR900004831B1 (ko)	1990-07-07	폴리시클릭퀴놀린, 나프티리딘 및 피라지노피리딘 유도체
US3949081A (en)	1976-04-06	4-Carbamoyl-1-benzazepines as antiinflammatory agents
NO157578B (no)	1988-01-04	Analogifremgangsmaate ved fremstilling av terapeutisk aktive imidazo(1,2-a)kinolinderivater
JPH06505021A (ja)	1994-06-09	ドラッグ及び物質の乱用による中毒の治療
DE69007904T2 (de)	1994-07-21	1-Oxa-2-oxo-8-azaspiro[4,5]decan-Derivate, Verfahren zu ihrer Herstellung und pharmazeutische Zusammensetzungen daraus.
JPH0242080A (ja)	1990-02-13	ヘテロ四環ラクタム誘導体
KR970005300B1 (ko)	1997-04-15	락탐 유도체
JP2000507254A (ja)	2000-06-13	アザスピロ誘導体
FR2508457A1 (fr)	1982-12-31	Pyrrolo(2,1-b)quinazolines et pyrido(2,1-b)quinazolines substituees, leur preparation et leurs utilisations therapeutiques
JPH06505698A (ja)	1994-06-30	新規化合物
US5380748A (en)	1995-01-10	Trialkylamine derivative and ameliorant for digestive tract movement containing the same
JPS604170A (ja)	1985-01-10	キノロン誘導体
BE898641A (fr)	1984-07-10	Nouvelles carboxy-thiazolo (3,2-a) pyrimidines substituees utiles notamment comme antiallergiques et leurs procedes de fabrication
KR800001144B1 (ko)	1980-10-14	2-(4-페닐-4-시아노부틸)-1,2,3,4-테트라하이드로-5(H)-피리도-[4,3-b]-인돌의 제조방법